Biosensors have been and are being developed to detect, identify and quantify various biochemicals, ranging from proteins to toxins to RNA to c-DNA to oligos and to disease agents such as viruses, bacteria, spores and Prions. This list is by way of example, and is not intended to be complete. Some biosensors sense charge on the molecule. Many biochemicals carry a net charge. Electrophoresis methods and various blots exploit molecule net charge to affect physical separation of such molecules.
There is a significant problem with existing techniques such as electrophoresis and the various blots. These sensors are not specific in identifying the molecules in question unless significant post processing and labeling is employed. Further, a very large quantity of the tested biochemical is required for electrophoresis detection methodologies.
In many instances the number of molecules available for detection is very small and may be below the sensitivity threshold of the sensor, or may be problematic with respect to sensitivity. For example, some plasma proteins are of very low concentration. Toxins such as Botulinum toxin are notoriously hard to detect at lethal thresholds because of their very low lethal and sub-lethal, but still dangerous, concentrations. Mass spectroscopy requires a large number of molecules in order to achieve adequate detection sensitivity.
In the case of c-DNA and RNA sensing, the number of base molecules present may be low for adequate detection and determination of which one is trying to specifically identify. This is possible if, for example, only a few bacteria are present or the RNA is of low concentration. Virus RNA may be of low density. Only a small portion of the RNA molecule may provide the definitive identification signature. Overall this can lead to a relatively small amount of RNA actually involved in the definitive detection process, if only few bacterial or viruses are present.
In the case of proteins, the target molecule concentration may be very low in the sample. For example, with Prions (mad cow disease), if a fluid sample is taken from an animal's blood, the target protein concentration may be very low. With a rapid infection of humans, animals or plants with disease, the initial signature indicators may be present in only very small concentrations. For the very early stages of cancer, when one wishes to identify disease presence, definitive indicators may be present in only very small concentrations. An example includes the four or so proteins reported as indicative of ovarian cancer. Where only small concentrations of target molecules are available, mass action effects can result in the bound target concentration being very low. A small percentage of the actual receptors or recognition units, specific antibodies, available for bonding results in a very small detection signal, for example, as is the case of a lethal concentration of botulinum toxin. At the very earliest onset of disease, the density of indicative proteins, viruses, antibodies and bacteria may be very low, requiring putting a very high sensitivity burden on the sensing approach.
Sensors for the detection of target molecules using charge and/or chemical potential have been reported. One of Applicant's most recent biosensor patents discusses sensing chemical potential, i.e., voltage. The most commonly used charge sensing to date are those using electrophoreses methods, such as the various blots. Semiconductor charge sensors have long been highly prized due to their compatibility with integrated circuits and attendant low cost manufacturing processes. An example is the ImmunoFET that uses a conventional MOSFET, absent a metal gate, and employing a reference electrode in solution.
Some sensors sense a change in charge or chemical potential as a result of a chemical attachment to the gate region of the devices. Needs exist for sensitive sensors that can sense very low concentrations.
Contamination and pollution in water, air and foodstuff is a continuing threat to public health. Water contaminated with Pb, Hg, Dioxin, or other hazardous chemical substances is problematic. Air may be contaminated with hazardous chemicals, of which OSHA has a long list, either in the general environment, the home, the industrial workplace or the chemical factory. Food contamination is likewise problematic for public heath. The chemicals in question may be inorganic (such as Pb and Hg), organic (such as organic solvents) or biochemical such as viruses, bacteria, toxins and hazardous proteins.
Additional environmental threats arise from potential chemical use by terrorists. Such threats include the well-known toxins such as botulinum toxin and ricin, as well as many others. Another threat is that of explosives intentionally (such as bombs introduced by terrorists) or unintentionally (such as antipersonnel mines) found in some location.
There is a need for an electronic sensor that can detect such public health risk chemicals in water, air and foodstuffs. In general, such requirements include biosensors that may incorporate such specific chemical binding means as oligos, proteins and antibodies, for example.